Antidiabetic activity of Anredera cordifolia (Ten.) Stennis extracts with different ethanol percentages: an evaluation based on in vitro, in vivo, and molecular studies Asri Sulfanti 1 , Nisrina Firdausi 2 , Nurhadi Nurhadi 2 , Ngatinem Ngatinem 2 , Kurnia Agustini 2 , Sri Ningsih 2,3 1 Research Center for Vaccine and Drugs Development, National Research and Innovation Agency (BRIN) Republic of Indonesia, South Tangerang, Indonesia 2 Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN) Republic of Indonesia, South Tangerang, Indonesia 3 Faculty of Medicine, Universitas Sultan Ageng Tirtayasa, Serang, Indonesia Corresponding author: Asri Sulfanti (asri.sulfanti@brin.go.id) Received 16 September 2022  ♦  Accepted 3 November 2022  ♦  Published 9 January 2023 Citation: Sulfanti A, Firdausi N, Nurhadi N, Ngatinem N, Agustini K, Ningsih S (2023) Antidiabetic activity of Anredera cordifolia (Ten.) Stennis extracts with diferent ethanol percentages: an evaluation based on in vitro, in vivo, and molecular studies. Pharmacia 70(1): 39–47. https://doi.org/10.3897/pharmacia.70.e94899 Abstract Anredera cordifolia (Ten.) Stennis, also known as Binahong (B), is an Indonesian plant used to treat diabetes. Te purpose of this study was to determine the best extragent for preparing Binahong extract as an antidiabetic agent using diferent concentrations of ethanol (50%, 70%, and 96%), labelled as BE50%, BE70%, and BE96%. An alpha-glucosidase inhibiting assay was used to assess the activity. Te most active extract was tested in vivo assay using an oral glucose tolerance test (OGTT) and alloxan-high feed diet (al- loxan-HFD)-induced diabetes in rats, with glucose level and beta cell Langerhans repair as parameters. A molecular assay was also performed to look into the expression of homeostasis regulator genes on 3T3-L1 adipose cells. Te results showed that 96% ethanol extract (BE96%) inhibited alpha-glucosidase the most efectively (IC 50 119.78± 11.14 μg/mL). Te in vivo assay revealed that the treatment BE96% at 250 mg/kg BW for 21 consecutive days signifcantly reduced plasma glucose levels in Type 2 DM rats compared to the control group (p ≤ .05) with improved of Langerhans beta cells. BE96% also signifcantly reduced postprandial glucose levels. At the cellular level, Oil-Red-O staining revealed that diferentiated adipocytes treated with BE96% had the highest lipid absorbance (p ≤ .05), compared to the control. BE96% signifcantly increased the expression of Glucose Transporter Isoform 4 (GLUT4) at the molecular level. It could be concluded that BE96% exhibited the best antidiabetic properties. Keywords Alloxan-HFD-induced diabetic rat, alpha-glucosidase inhibition activity, Binahong, glucose tolerance test, GLUT4 expression Introduction A metabolic condition known as diabetes mellitus (DM) is characterized by chronically high blood sugar levels (hyperglycemia) and blood insulin levels (hyperinsulin- emia) (Westman 2021). In the majority of the developed and emerging nations, DM is a serious issue. According to estimates, there would be approximately 463 million cases Copyright Sulfianti A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pharmacia 70(1): 39–47 DOI 10.3897/pharmacia.70.e94899 Research Article